反応 #1095116

反応方程式

oxalyl chloride

hydrochloric acid

hydrochloric acid

2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid

DL-alaninol

→

2-{[2-(2-benzo[b]thiophen-5-ylethoxy)ethyl]amino}-1-propanol

溶媒

tetrahydrofuran

tetrahydrofuran

N,N-dimethylformamide

methylene chloride

triethylamine

反応条件

後処理

1. 1
   workup.ADDITIONare added to the solution
2. 2
   その他obtained above, and the mixture
3. 3
   温度After cooling the mixture to −50° C.
4. 4
   その他the mixture thus formed
5. 5
   workup.STIRRINGis stirred at ambient temperature for 4 hours
6. 6
   その他the organic layer is separated
7. 7
   洗浄The organic layer is washed with saturated aqueous solution of sodium chloride
8. 8
   乾燥dried over anhydrous magnesium sulfate
9. 9
   workup.DISTILLATIONthe solvent is distilled off under reduced pressure
10. 10
    その他The residue thus obtained
11. 11
    温度cooled with ice, to which
12. 12
    その他The mixture thus obtained
13. 13
    workup.STIRRINGis stirred at ambient temperature for 13 hours
14. 14
    温度heated
15. 15
    温度under reflux for one hour
16. 16
    温度After cooling the reaction mixture
17. 17
    workup.DISTILLATIONthe solvent is distilled off under reduced pressure, water and ethyl acetate
18. 18
    workup.ADDITIONare added to the residue
19. 19
    その他the aqueous layer is separated
20. 20
    workup.ADDITIONEthyl acetate is added to the aqueous layer
21. 21
    その他the organic layer is separated
22. 22
    その他The organic layer thus obtained
23. 23
    洗浄is washed with saturated aqueous solution of sodium chloride
24. 24
    乾燥dried over anhydrous magnesium sulfate
25. 25
    workup.DISTILLATIONthe solvent is distilled off under reduced pressure
26. 26
    その他an oily residue thus obtained
27. 27
    その他is purified by column chromatography (eluent: chloroform:methanol=40:1 to 30:1)

実験手順

In 10 mL of methylene chloride is dissolved 1.0 g of 2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid. At an ice-cooled temperature, 0.41 mL of oxalyl chloride and 0.1 mL of N,N-dimethylformamide are added to the solution obtained above, and the mixture is stirred at ambient temperature for 1.5 hours. After cooling the mixture to −50° C., 0.41 mL of DL-alaninol and 1.77 mL of triethylamine are dropwise added, and the mixture thus formed is stirred at ambient temperature for 4 hours. Ice water is added to the reaction mixture, pH is adjusted to 1 with 6 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue thus obtained is dissolved in 10 mL of tetrahydrofuran and cooled with ice, to which is dropwise added 16.9 mL of 1 mol/L solution of borane-tetrahydrofuran complex in tetrahydrofuran. The mixture thus obtained is stirred at ambient temperature for 13 hours. The reaction mixture is acidified with 5.6 mL of 6 mol/L hydrochloric acid and heated under reflux for one hour. After cooling the reaction mixture, the solvent is distilled off under reduced pressure, water and ethyl acetate are added to the residue, and the aqueous layer is separated. Ethyl acetate is added to the aqueous layer, pH is adjusted to 9.5 with 50% aqueous solution of sodium hydroxide, and the organic layer is separated. The organic layer thus obtained is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and an oily residue thus obtained is purified by column chromatography (eluent: chloroform:methanol=40:1 to 30:1) to obtain 0.80 g of 2-{[2-(2-benzo[b]thiophen-5-ylethoxy)ethyl]amino}-1-propanol as a light yellow-colored oily product.

出典